AMPA receptors are present on mouse lymphocytes and AMPA receptor antagonist, GYKI-52466, inhibits lymphocyte proliferation. (50.31)

Abstract

Abstract AMPA receptors are glutamate-gated ion channels canonically found on mammalian neurons for excitatory neurotransmission. AMPA receptors are composed of a tetrameric combination of subunits, GluR1-4, in the form of a homo or hetero dimers. The presence of a post-transcriptionally edited GluR2 subunit confers Ca++ impermeability to the ion channel. Because treatment of mice with viral encephalitis with AMPA receptor antagonists inhibits inflammation and protects from fatal paralysis, we studied the presence and function of AMPA receptors on lymphocytes. Using RT-PCR and restriction digest assays of mRNAs obtained from mouse spleen cells, we showed the presence of unedited mRNA for Ca++-permeable GluR2 and for variants with alternative splicing patterns. Using an in vitro CFSE proliferation assay with plate bound anti-CD3/CD28 we showed that the noncompetitive AMPA receptor antagonist, GYKI-52466, suppresses T-cell receptor CD3+ lymphocyte proliferation in a dose dependent manner, with the greatest effect on CD4+ T-cells. Decreased proliferation correlated with decreased production of IL-2. Lymphocytes treated with GYKI-52466 did not show an increase in cell death compared to controls. These studies show that AMPA receptors are present on lymphocytes and participate in the proliferative response to signaling through the T-cell receptor.